Between 400,000 and 450,000 people are estimated to experience sudden cardiac death out of hospital or in the emergency room each year in the United States. Brain damage is a major cause of morbidity and mortality in these patients with most never regaining consciousness. Safe and effective therapies that improve outcome after cardiac arrest are urgently needed. Even with delays of 4 to 8 h to achieve target temperatures, induced mild hypothermia (32-34:C) in patients resuscitated from out-of-hospital ventricular fibrillation (VF) improved neurologic recovery and survival. Despite this evidence, induced hypothermia is not widely used, and its efficacy in patients with other initial rhythms is largely unstudied. Results from animal models suggest that efficacy of mild hypothermia would improve if initiated as soon as possible after return of spontaneous circulation (ROSC). The overall goal of this study is to determine whether a strategy of field cooling improves outcome after out-of-hospital cardiac arrest. To this end, we will randomize 1364 eligible (achieving ROSC but still comatose) patients with treated out-of-hospital for cardiac arrest (both VF and non-VF) to standard care with or without field cooling initiated immediately by paramedics following ROSC. Field cooling will be achieved with intravenous infusion of 2 liters of 4:C normal saline over 20 to 30 minutes, sedation, and muscle paralysis. Outcome will be based on the endpoint: 'awake at hospital discharge'. Since hospital cooling could potentially modify or confound the effect of field cooling, both randomization and analysis will be stratified by whether or not the intended receiving hospital has a routine cooling protocol. Because of the American Heart Association (AHA) guidelines, most hospitals in the study area routinely cool comatose patients with ROSC whose initial rhythm was VF. Such hospitals do not generally cool similar patients whose initial rhythm was not VF, though this is somewhat variable. A few hospitals do not cool. Data will be collected from review of paramedic run reports, hospital records, and 3- month telephone follow-up interview. We propose the following specific aims: Aim 1: Determine outcome of field cooling in eligible patients whose initial rhythm is VF and intended to be delivered to a cooling hospital. Aim 2: Examine safety of field cooling in eligible patients whose initial rhythm is not VF, i.e., pulseless electrical activity or asystole Aim 3: Compare the outcome differences in VF patients delivered to non-cooling hospitals with the differences found in the primary comparison population, VF patients delivered to cooling hospitals. PUBLIC HEALTH RELEVANCE: Between 400,000 and 450,000 people are estimated to experience sudden cardiac death out of hospital or in the emergency room each year in the United States. Brain damage is a major cause of morbidity and mortality in these patients with most never regaining consciousness. Safe and effective therapies that improve outcome after cardiac arrest are urgently needed and in this grant proposal we aim to determine whether the application of mild hypothermia using a rapid infusion of cold normal saline will improve outcome in patients who suffer out-of-hospital cardiac arrest.